Study of Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification

NCT02626364 | Completed Phase 2

• 1 other identifier: ARO-015
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof of concept, single-arm study to investigate crenolanib monotherapy in patients with recurrent/refractory glioblastoma with PDGFRA gene amplification by assessing the progression-free survival (PFS) at 6 months. Crenolanib will be given orally starting at 100 mg TID continuously until disease progression, unacceptable toxicity, or consent withdrawal.

Conditions

Recurrent/Refractory Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 6 months

  6 months

Secondary Outcomes (4)

• Overall response rate by RANO criteria

  1 year

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  2 years

• Change in symptom burden using The MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)

  2 years

• Overall survival

  3 years

Other Outcomes (1)

• Duration of response

  2 years

Study Arms (1)

Treatment

EXPERIMENTAL

crenolanib 100mg PO TID

Drug: crenolanib

Interventions

crenolanib DRUG

single-agent crenolanib at 100 mg PO TID

Also known as: CP-868,596-26

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (male or female) ≥ 18 years of age.
• Histopathologically confirmed glioblastoma or gliosarcoma (WHO Grade IV) confirmed by local pathology tissue screening.
• Radiologic evidence of first recurrence after initial treatment (including surgery, radiation, and temozolomide) or tumor refractory to initial treatment without subsequent treatment in glioblastoma or gliosarcoma (WHO Grade IV). Transformation from a lower grade glioma previously treated with radiation and/or temozolomide to glioblastoma will be considered first recurrence for the purpose of this trial
• Tumor tissue available from original diagnosis and/or recurrence; a minimum of 1 FFPE archival tumor tissue block (preferred) or a minimum of 20 FFPE unstained slides from initial and/or most recent pre-registration biopsy or resection. It is recommended that at least 1 cm\^2 of tissue composed primarily (defined as greater than 85%) of tumor is present.
• Confirmed PDGFRA amplification in the tumor tissue at the time of diagnosis or time of recurrence. Central confirmation of PDGFRA amplification will be performed by FISH in CLIA certified lab (ProPath). Signal quantitation will be used to generate a PDGFRA/centromere 4 ratio. PDGFRA to Centromere 4 ratios will be interpreted as follows: 1.8 to 2.2, borderline for amplification; 2.2 to 5.0, low-level amplification; and greater than 5.0 or clustered signals that are too numerous to count would be considered highly amplified. Tumor samples with PDGFRA to Centromere 4 ratios of 2.2 or higher will be considered amplified and therefore eligible for this trial. For patients with local CLIA testing demonstrating PDGFRA amplification by Next Generation Sequencing (Foundation Medicine, CMS400), central testing will not be required.
• Patients must have adequate organ function at baseline as defined below:
• Adequate liver function (within 7 days of crenolanib commencement), as determined by:
• Serum ALT, AST ≤ 2 × ULN
• Normal serum total bilirubin (lower and upper limits of local Laboratory)
• Adequate renal function assessed by: serum creatinine ≤ 1.5 × ULN
• KPS ≥ 60
• Recovered (returned to ≤ grade 1 as per CTCAE v4.03) from prior treatment-related toxicity.
• A minimum of 3 weeks must have elapsed from last intake of prior standard chemotherapy treatment.
• A minimum of 6 weeks must have elapsed from the last dose of nitrosoureas.
• A minimum of 5 half-lives of last dose of investigational agent must have elapsed prior to C1D1.

You may not qualify if:

• Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
• Known positive for HIV
• Patients previously treated with bevacizumab.
• NYHA Class III-IV heart failure, myocardial infarction \<6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
• Patients receiving concurrent anti-cancer treatment (chemotherapy, investigational agents, immunotherapy, endocrine therapy, or Optune®…)
• Patients with any other severe and/or uncontrolled concurrent disease affecting the cardiovascular system, liver, kidneys, hematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures/results or compromise compliance with the protocol.
• Pregnant or breast-feeding women.
• Patients unable to swallow pills.
• Patients who are allergic to MRI contrast medium or unable to undergo MRI for any other reason.
• Patients unable to provide informed consent.
• Patients on EIADs are not eligible, unless the antiepileptic drug can be safely tapered and discontinued before C1D1.

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 75243, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

crenolanib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Barbara O'Brien, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: December 10, 2015
• Study Start: April 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 20, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)